Publications by authors named "Rui Peng"

299 Publications

Force sensing in a dual-mode optomechanical system with linear-quadratic coupling and modulated photon hopping.

Opt Lett 2021 Jul;46(13):3075-3078

A weak force sensor scheme is presented in an optomechanical system, in which the two cavity modes couple to a mechanical mode with linear and quadratic coupling. Due to introducing time-dependent hopping, the linear and quadratic coupling terms coexist under the rotating-wave approximation in the interaction picture. Compared with the quantum non-demolition measurement (ignoring the quadratic optomechanical coupling), the current scheme can decrease the additional noise to a lower level. Our proposal provides a promising platform for improving the detection of a weak force.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.425484DOI Listing
July 2021

Force sensing in a dual-mode optomechanical system with linear-quadratic coupling and modulated photon hopping.

Opt Lett 2021 Jul;46(13):3075-3078

A weak force sensor scheme is presented in an optomechanical system, in which the two cavity modes couple to a mechanical mode with linear and quadratic coupling. Due to introducing time-dependent hopping, the linear and quadratic coupling terms coexist under the rotating-wave approximation in the interaction picture. Compared with the quantum non-demolition measurement (ignoring the quadratic optomechanical coupling), the current scheme can decrease the additional noise to a lower level. Our proposal provides a promising platform for improving the detection of a weak force.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.425484DOI Listing
July 2021

Optimal Product Substitution and Dual Sourcing Strategy considering Reliability of Production Lines.

Reliab Eng Syst Saf 2020 Oct 23;202:107037. Epub 2020 May 23.

Kent Business School, University of Kent, Canterbury, Kent CT2 7FS, United Kingdom.

Most of the supply chain literature assumes that product substitution is an effective method to mitigate supply chain disruptions and that all production lines either survive or are disrupted together. Such assumptions, however, may not hold in the real world: (1) when there is a shortfall of all products, product substitution may be inadequate unless it is paired with other strategies such as dual sourcing; and (2) production lines do not survive forever and may fail. To relax such assumptions, this paper therefore investigates the situations that the manufacturer may optimize substitution policy and dual sourcing policy to cope with supply chain disruptions. The paper obtains and compares the optimal policies for both deterministic and stochastic demands. A real-world case is also studied to verify the effectiveness of the proposed model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ress.2020.107037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255351PMC
October 2020

LINC00665/miR-379-5p/GRP78 regulates cisplatin sensitivity in gastric cancer by modulating endoplasmic reticulum stress.

Cytotechnology 2021 Jun 26;73(3):413-422. Epub 2021 Apr 26.

Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210029 Jiangsu Province China.

Acquired resistance to cisplatin (DDP)-based chemotherapy greatly hinders the treatment of gastric cancer (GC). LINC00665 serves as an oncogene in GC. Hence, the current study was designed to investigate the regulatory effects of LINC00665 on DDP-resistance of GC. LINC00665 and miR-379-5p expression levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and Glucose regulated protein 78 (GRP78) protein level was measured by western blot assay. Interactions between LINC00665 and miR-379-5p or between miR-379-5p and GRP78 were verified by dual luciferase reporter assay. Cell counting kit 8 (CCK-8) assay and flow cytometry assay respectively determine the proliferative ability and apoptosis of GC cells. Western blot analysis was also performed to detect the protein levels of C/EBP-homologous protein (CHOP), X box binding protein (XBP1) and apoptosis-related proteins. In addition, GRP78 expression was evaluated by immunofluorescence. It was observed that the expression levels of LINC00665 and GRP78 were upregulated, and the expression level of miR-379-5p was downregulated in DDP-sensitive and DDP-resistant GC cell lines. What's more, GRP78 expression and the cell growth inhibition rates of DDP-sensitive and DDP-resistant GC cells had a negative correlation. Additionally, miR-379-5p was a target miRNA of LINC00665, and GRP78 was a target mRNA of miR-379-5p. Functional studies revealed that knockdown of LINC00665 inhibited DDP-resistant GC cell proliferation, induced apoptosis as well as suppressed Endoplasmic reticulum (ER) stress. Mechanistically, knockdown of LINC00665 downregulated GRP78 expression by strengthening miR-379-5p. LINC00665 silencing could overcome DPP-resistance of GC cells by downregulating GRP78 via sponging miR-379-5p, indicating that LINC00665 might be a potential therapeutic target for DDP- resistant GC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10616-021-00466-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167010PMC
June 2021

LHCGR and ALMS1 defects likely cooperate in the development of polycystic ovary syndrome indicated by double-mutant mice.

J Genet Genomics 2021 May 1. Epub 2021 May 1.

Children's Hospital, Institutes of Reproduction and Development, Fudan University, Shanghai 201102, China; Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200011, China. Electronic address:

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with evidence of polygenetic components, and obesity may be a risk factor for hyperandrogenism. Previous studies have shown that LHCGR is enriched in the ovary and LHCGR deficiency causes infertility without typical PCOS phenotypes. ALMS1 is implicated in obesity and hyperandrogenism, the common phenotypes among PCOS patients. Through whole-exome sequencing of 22 PCOS families and targeted candidate gene sequencing of additional 65 sporadic PCOS patients, we identified potential causative mutations in LHCGR and ALMS1 in a sibling-pair PCOS family and three sporadic PCOS patients. The expression of LHCGR in granulosa-like tumor cell line (KGN) cells promoted cyclic adenosine monophosphate production and granulosa cell proliferation, indicating that LHCGR is an activating mutation. Lhcgr mice showed an irregular estrous cycle, reduced follicles with dynamic folliculogenesis, and increased testosterone (T), estradiol (E2), and dehydroepiandrosterone. LhcgrAlms1 mice displayed increased T and E2 but decreased late secondary and preovulatory follicles. We showed that activating mutation of LHCGR likely plays important roles in the pathophysiology of PCOS involving abnormal reproductive physiology, whereas ALMS1 deficiency may promote anovulatory infertility via elevated androgens, suggesting that the disturbed LHCGR and ALMS1 cooperatively induce PCOS phenotypes, characterized as anovulation and hyperandrogenemia frequently observed in PCOS patients with obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgg.2021.03.014DOI Listing
May 2021

Impact of measuring distance and exposure to cold outdoor environment on the temperature measurement using a non-contact infrared thermometer.

Chin Med J (Engl) 2021 May 28. Epub 2021 May 28.

Department of Dermatology, Peking University First Hospital; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses; National Clinical Research Center for Skin and Immune Diseases, Beijing 100034, China Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada Department of Biomedical Statistics, Peking University First Hospital, Beijing 100034, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CM9.0000000000001546DOI Listing
May 2021

Evolution of spin excitations from bulk to monolayer FeSe.

Nat Commun 2021 May 25;12(1):3122. Epub 2021 May 25.

Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA.

In ultrathin films of FeSe grown on SrTiO (FeSe/STO), the superconducting transition temperature T is increased by almost an order of magnitude, raising questions on the pairing mechanism. As in other superconductors, antiferromagnetic spin fluctuations have been proposed to mediate SC making it essential to study the evolution of the spin dynamics of FeSe from the bulk to the ultrathin limit. Here, we investigate the spin excitations in bulk and monolayer FeSe/STO using resonant inelastic x-ray scattering (RIXS) and quantum Monte Carlo (QMC) calculations. Despite the absence of long-range magnetic order, bulk FeSe displays dispersive magnetic excitations reminiscent of other Fe-pnictides. Conversely, the spin excitations in FeSe/STO are gapped, dispersionless, and significantly hardened relative to its bulk counterpart. By comparing our RIXS results with simulations of a bilayer Hubbard model, we connect the evolution of the spin excitations to the Fermiology of the two systems revealing a remarkable reconfiguration of spin excitations in FeSe/STO, essential to understand the role of spin fluctuations in the pairing mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-23317-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149670PMC
May 2021

Inhibition mechanism and antibacterial activity of natural antibacterial agent citral on bamboo mould and its anti-mildew effect on bamboo.

R Soc Open Sci 2021 Apr 21;8(4):202244. Epub 2021 Apr 21.

School of Engineering, Zhejiang A&F University, Hangzhou 311300, People's Republic of China.

Bamboo, a natural material, has been widely used in the fields of decoration, architecture and furniture. However, bamboo is easy to mildew and lose its use value. In this paper, the inhibition mechanism and antibacterial activity of a natural antibacterial agent citral on bamboo mould and its anti-mildew effect on bamboo were studied. The results showed that citral could change the shape of mycelium, destroy the integrity of mycelium structure, cell wall and cell membrane structure, thereby causing leakage of nucleic acids, proteins and other substances in the cell, as well as destroy the pH balance of the inside and outside of the cell, to inhibit or kill mould. When the concentration of citral is 100 mg ml, the antibacterial rates of citral against (PC), (TV), (AN) and a hybrid fungi group comprising PC, TV and AN (Hun) were more than 100%. However, compared with the direct effect of citral on mould, the antibacterial property of bamboo treated with citral was significantly reduced, the mildew proof effect can be achieved only if the concentration of citral to treat bamboo is increased to more than twice the concentration of citral directly acting on mould.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rsos.202244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059595PMC
April 2021

Systematic Identification of Survival-Associated Alternative Splicing Events in Kidney Renal Clear Cell Carcinoma.

Comput Math Methods Med 2021 19;2021:5576933. Epub 2021 Apr 19.

Laboratory of Tissue and Cell Biology, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing, China.

There is growing evidence that aberrant alternative splicing (AS) is highly correlated with driving tumorigenesis, but its function in kidney renal clear cell carcinoma (KIRC) remains to be discovered. In this study, we obtained the level-3 RNA sequencing and clinical data of KIRC from The Cancer Genome Atlas (TGCA). Combining with the splicing event detail information from TGCA SpliceSeq database, we established the independent prognosis signatures for KIRC with the univariate and multivariate Cox regression analyses. Then, we used the Kaplan-Meier analysis and receiver operating characteristic curves (ROCs) to assess the accuracy of prognosis signatures. We also constructed the regulatory network of splicing factors (SFs) and AS events. Our results showed that a total of 12029 survival-associated AS events of 5761 genes were found in 524 KIRC patients. All types of prognosis signatures displayed a satisfactory ability to reliably predict, especially in exon skip model which the area under curve of ROC was 0.802. Moreover, 18 splicing factors (SFs) highly correlated to AS events were identified. With the construction of the SF-AS interactive network, we found that SF powerfully promotes the occurrence of abnormal AS and may have a profound role in KIRC. Collectively, we screened survival-associated AS events and established prognosis signatures for KIRC, coupling with the SF-AS interactive network, which might provide a key perspective to clarify the potential mechanism of AS in KIRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5576933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075682PMC
April 2021

Nitrite-enhanced copper-based Fenton reactions for biofilm removal.

Chem Commun (Camb) 2021 Jun;57(45):5514-5517

Department of Chemistry, Cape Breton University, Sydney, Nova Scotia B1P 6L2, Canada.

Unwanted biofilms present challenges for many industries. Herein an innovative biofilm removal technology was developed based on nitrite-accelerated Fenton chemistry, where both dissolved Cu ions and nano-CuO surfaces efficiently generate reactive nitrogen species as disinfectants. This simple, efficient, and cost-effective approach for biofilm removal generates important insights into Fenton chemistry, a fundamental mechanism in nature, considering the ubiquity of copper, hydrogen peroxide, and nitrite in the environment, biological systems, and various industrial processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cc00374gDOI Listing
June 2021

RNA-Seq analysis reveals critical transcriptome changes caused by sodium butyrate in DN mouse models.

Biosci Rep 2021 Apr;41(4)

Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China.

Diabetic nephropathy (DN)-a common complication of diabetes-is the primary cause of end-stage renal disease. Sodium butyrate (NaB) is a short-chain fatty acid (SCFA) that is a metabolic product of intestinal bacterium, and its protective effect on the kidney has been reported in cases of DN. However, its underlying mechanism remains unclear. The aim of the present study was to investigate the effect of NaB on globe transcriptome changes in DN. In our study, 8-week-old male db/db mice suffering from DN were randomly divided into two groups: the DN+NaB group (DN mice treated with NaB, 5 g/kg/day) and the DN group (DN mice treated with saline). Further, normal db/m mice were used as the normal control (NC) group. The blood glucose, body weight, urinary microalbumin and urinary creatinine of mice were measured for all three groups. Whole-transcriptome analysis was performed by RNA sequencing (RNA-Seq) to evaluate the profiling of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs). Bioinformatics analysis was performed to predict the potential NaB-related lncRNAs and genes in DN. The expressions of lncRNAs and mRNAs were tested using the quantitative real-time polymerase chain reactions (qRT-PCRs) in renal tissues and mesangial cells treated with NaB. The results of the present study demonstrated that NaB ameliorated renal dysfunction in DN mice. Moreover, RNA-Seq results identified that some lncRNAs and mRNAs were reversely changed in the DN+NaB group in comparison to those in the DN group. Additionally, the integrated co-expression networks of NaB-related lncRNAs revealed that these lncRNAs interacted with 155 key mRNAs. Furthermore, the co-expression network of inflammation-related lncRNAs and mRNAs demonstrated that those reversed lncRNAs and mRNAs also play essential roles in the inflammatory response. In summary, the present study suggests that NaB ameliorates diabetes-induced renal dysfunction and regulates transcriptome changes in DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BSR20203005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035627PMC
April 2021

Associations Between Tenascin-C and Testosterone Deficiency in Men with Major Depressive Disorder: A Cross-Sectional Retrospective Study.

Authors:
Rui Peng Yan Li

J Inflamm Res 2021 16;14:897-905. Epub 2021 Mar 16.

Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, People's Republic of China.

Background: Elevated levels of tenascin-C are linked to increased risk and severity of major depressive disorder (MDD), while testosterone shows a protective effect. The present study explored associations between serum levels of tenascin-C and testosterone in Chinese men with MDD.

Methods: Testosterone and tenascin-C levels were measured in sera of 412 men with MDD and 237 age- and sex-matched controls. Serum levels of thyroid hormone, lipids, and high-sensitivity C-reactive protein (hs-CRP) were also quantified. Potential associations were examined using covariance, subgroup analysis, and multivariate linear regression analyses.

Results: Significantly higher concentrations of tenascin-C were detected in sera of subjects with MDD than in controls. Among subjects with MDD, testosterone concentrations inversely correlated with tenascin-C levels. This relationship was observed when patients were stratified by age at onset; duration or severity of depression; or concentration of thyroid hormones, low- or high-density lipoprotein, or hs-CRP. The negative association remained even when the statistical model was adjusted for age, smoking status, alcohol use, and body mass index. Linear regression with bootstrap resampling confirmed that high tenascin-C levels inversely correlated with testosterone levels.

Conclusion: In men with MDD, high tenascin-C concentrations correlate with testosterone deficiency. The combination of elevated tenascin-C and testosterone deficiency may be associated with MDD progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JIR.S298270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981168PMC
March 2021

RNA-sequencing reveals plantar keloid has potential bone/cartilage characteristics.

Exp Dermatol 2021 Jul 18;30(7):997-998. Epub 2021 Apr 18.

Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/exd.14333DOI Listing
July 2021

Identification of potential oncogenes in triple-negative breast cancer based on bioinformatics analyses.

Oncol Lett 2021 May 10;21(5):363. Epub 2021 Mar 10.

Department of Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.

Triple-negative breast cancer (TNBC) is a subtype with high rates of metastasis, poor prognosis and limited therapeutic options. The present study aimed to identify the potential pivotal genes for prognosis and treatment in TNBC. A total of two microarray expression datasets, GSE38959 and GSE65212, were downloaded from the Gene Expression Omnibus database, and RNA-sequencing data of breast cancer from The Cancer Genome Atlas database were analyzed to screen out differentially expressed genes (DEGs) between TNBC tissues and normal tissues. The intersection of DEGs was submitted to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. A protein-protein interaction (PPI) network was constructed and visualized using Cytoscape software. Furthermore, module, centrality and survival analyses were performed to identify the potential hub genes. Reverse transcription-quantitative (RT-q)PCR analysis was performed to detect the expression levels of key genes in TNBC samples, and 377 DEGs were identified. Functional analysis revealed that the DEGs were significantly involved in cell cycle process, nuclear division and the p53 signaling pathway. A PPI network was constructed with these DEGs, and 66 core genes with high centrality features in module 1 were selected. Relapse-free survival analysis confirmed that high expression levels of five genes [cyclin B1 (CCNB1), GINS complex subunit 2, non-SMC condensin I complex subunit G (NCAPG), minichromosome maintenance 4 (MCM4) and ribonucleotide reductase regulatory subunit M2 (RRM2)] were significantly associated with poor prognosis in TNBC. RT-qPCR analysis demonstrated that CCNB1, NCAPG, MCM4 and RRM2 were significantly upregulated in 25 TNBC tissues compared with adjacent normal breast tissues. Furthermore, gene set enrichment analysis revealed that CCNB1, NCAPG, MCM4 and RRM2 were closely associated with tumor proliferation. Taken together, these results suggest that CCNB1, NCAPG, MCM4 and RRM2 are associated with tumorigenesis and TNBC progression, and thus may act as promising prognostic biomarkers and therapeutic targets for TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2021.12624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967975PMC
May 2021

Identification and Validation of Key Genes in Hepatocellular Carcinoma by Bioinformatics Analysis.

Biomed Res Int 2021 23;2021:6662114. Epub 2021 Feb 23.

Department of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and has poor outcomes. However, the potential molecular biological process underpinning the occurrence and development of HCC is still largely unknown. The purpose of this study was to identify the core genes related to HCC and explore their potential molecular events using bioinformatics methods. HCC-related expression profiles GSE25097 and GSE84005 were selected from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) between 306 HCC tissues and 281 corresponding noncancerous tissues were identified using GEO2R online tools. The protein-protein interaction network (PPIN) was constructed and visualized using the STRING database. Gene Ontology (GO) and KEGG pathway enrichment analyses of the DEGs were carried out using DAVID 6.8 and KOBAS 3.0. Additionally, module analysis and centrality parameter analysis were performed by Cytoscape. The expression differences of key genes in normal hepatocyte cells and HCC cells were verified by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). Additionally, survival analysis of key genes was performed by GEPIA. Our results showed that a total of 291 DEGs were identified including 99 upregulated genes and 192 downregulated genes. Our results showed that the PPIN of HCC was made up of 287 nodes and 2527 edges. GO analysis showed that these genes were mainly enriched in the molecular function of protein binding. Additionally, KEGG pathway analysis also revealed that DEGs were mainly involved in the metabolic, cell cycle, and chemical carcinogenesis pathways. Interestingly, a significant module with high centrality features including 10 key genes was found. Among these, CDK1, NDC80, HMMR, CDKN3, and PTTG1, which were only upregulated in HCC patients, have attracted much attention. Furthermore, qRT-PCR also confirmed the upregulation of these five key genes in the normal human hepatocyte cell line (HL-7702) and HCC cell lines (SMMC-7721, MHCC-97L, and MHCC-97H); patients with upregulated expression of these five key genes had significantly poorer survival and prognosis. CDK1, NDC80, HMMR, CDKN3, and PTTG1 can be used as molecular markers for HCC. This finding provides potential strategies for clinical diagnosis, accurate treatment, and prognosis analysis of liver cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6662114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925030PMC
May 2021

Real-World Data on Osimertinib in Chinese Patients with Pretreated, EGFR T790M Mutation Positive, Advanced Non-Small Cell Lung Cancer: A Retrospective Study.

Cancer Manag Res 2021 26;13:2033-2039. Epub 2021 Feb 26.

Department of Oncology, Affiliated Qingdao Central Hospital, Qingdao University, Qingdao, Shandong, People's Republic of China.

Purpose: As a third-generation EGFR TKI has been taken orally, Osimertinib effectively inhibits mutant EGFR, including T790M EGFR resistance mutations. Here, we examined real-world efficacy and tolerability of Osimertinib among Chinese patients with advanced EGFR T790M-mutant NSCLC.

Patients And Methods: A total of 106 advanced NSCLC patients who were taking Osimertinib following disease progression after EGFR-TKIs or other treatments were retrospectively recruited in this study. The PFS and OS after Osimertinib treatment were analyzed as the primary endpoints.

Results: Osimertinib was used as a second line and ≥3rd line treatment in 22.6% and 77.4% of the patients, respectively. DCR and ORR were 93.4% and 57.5%, respectively. Median PFS was 12.4 12 (95% CI, 10.5-13.5) months. The PFS was 11 (8.0, 14.0) and 12 (10.3,13.7) months ( = 0.373), in patients with and without CNS metastasis, respectively. PFS in 2nd and ≥3rd line treatment was 11 (9.0, 13.0) and 12.4 12 (8.9, 15.1) months ( = 0.799), respectively. In patients with EGFR exon 19 deletion and exon 21 L858 mutation, the median PFS was 11 (9.2, 12.8) and 12 (9.2, 14.8) months, respectively ( = 0.833). Median PFS in the monotherapy group and combined anti-angiogenesis group was 11 (9.9,12.1) and 14 (11.2,16.8) months, respectively. Median OS after Osimertinib initiation was 27 (19.6, 34.4) months: 15 (6.9, 23.1) and 27 (22, 32) months in patients with and without CNS metastasis (p=0.027), 27 (20.3,33.7) months and (undefined) as second line or ≥3rd line of treatment ( = 0.421), respectively. In patients with exon 19 deletion, the median OS was not reached, and in patients with exon 21 L858 mutations, the median OS was 23 (19.1,29.9) months (p=0.027). Median OS in the monotherapy group was 27 (21.7,32.3) months, and in combined anti-angiogenesis group was not reached (p=0.68).

Conclusion: Osimertinib can effectively treat advanced NSCLC with T790M mutations independently of previous treatment lines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S287466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926038PMC
February 2021

Effects of tonifying kidney and strengthen bone therapy on non-dialysis patients with chronic kidney disease-mineral and bone disorder: A protocol for the systematic review and meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2021 Feb;100(6):e24445

College of Acupuncture and Orthopedics.

Background: Correction of calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) disorders is the standard of treatment in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), but the side effects and adverse reactions brought by western medicine (WM) are still the main problems. More importantly, the lack of protection of kidney function in the treatment greatly affects the health of patients. Although traditional Chinese medicine (TCM), specifically tonifying kidney and strengthen bone (TKSB) therapy is wildly applied for patients with CKD-MBD in China, the evidence of TKSB therapy in the treatment of CKD-MBD is limited. Thus, we pretent to conduct this protocol to evaluate the efficacy and safety of TKSB therapy combined with WM for non-dialysis patients with CKD-MBD.

Methods: A system research of randomized controlled trials (RCTs) of TKSB therapy for CKD-MBD will be conducted by 2 investigators from 7 electronic databases. Methodological quality evaluations will be performed by using the Cochrane collaboration tool and data analysis will be conducted by RevMan V5.3 software and STATA v15.0.

Results: The results of this paper will be submitted to a peer-reviewed journal for publication.

Conclusion: This research will determine the safety and efficacy of TKSB therapy in treating non-dialysis patients with CKD-MBD.

Inplasy Registration Number: INPLASY2020120086.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886426PMC
February 2021

Repressing PDCD4 activates JNK/ABCG2 pathway to induce chemoresistance to fluorouracil in colorectal cancer cells.

Ann Transl Med 2021 Jan;9(2):114

College of Life Sciences, Sichuan University, Chengdu, China.

Background: Colorectal cancer (CRC) is the third major cause of cancer-related death worldwide, and fluorouracil (5-FU) is widely used in the treatment of CRC. However, acquired resistance to 5-FU has become an obstacle in the effective treatment of CRC. Adenosine triphosphate (ATP)-binding cassette sub-family G member 2 (ABCG2) has been found highly expressed in CRC patients with poor responsiveness to folinic acid/5-FU/irinotecan. However, the mechanisms of 5-FU resistance regulated by ABCG2 in CRC cells remain to be comprehensively understood. We aimed to explore the upstream mechanisms of ABCG2 involved in the regulation of chemoresistance in CRC cells.

Methods: We investigated the potential mechanisms of 5-FU resistance in HCT116, RKO, RKO microRNA-21 (miR-21) knockout, and acquired 5-FU-resistant HCT116 (HCT116/FUR) cells. The biochemical and biological analyses were conducted using semiquantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, transfections, and rescue experiments, along with cell proliferation, viability, and colony formation assays. In order to investigate the efficacy of inhibiting the c-Jun NH2 terminal kinase (JNK) pathway to overcome 5-FU resistance, HCT116 and 5-FU-resistant HCT116 cells were inoculated into BALB/c-nu/nu mice to establish the cell-derived xenograft model.

Results: The results showed that ABCG2 expression in HCT116/FUR cells was higher compared to HCT116 cells. Overexpression of ABCG2 decreased sensitivity to 5-FU in HCT116 cells, but knockdown of ABCG2 decreased the survival rate in HCT116/FUR cells. Additionally, repressing programmed cell death 4 (PDCD4) activated the JNK pathway in HCT116/FUR cells. Overexpression of PDCD4 inhibited phosphorylation of c-Jun and ABCG2 expression, and recovered sensitivity to 5-FU in HCT116/FUR cells. Moreover, treatment with the JNK pathway inhibitor SP600125 downregulated ABCG2 expression and rescued sensitivity to 5-FU in HCT116/FUR cells. We also found that miR-21 expression in HCT116/FUR cells was higher compared to HCT116 cells. Finally, 5-FU treatment in combination with SP600125 significantly decreased tumorigenicity compared to other treatments .

Conclusions: Our results demonstrated that 5-FU treatment upregulated miR-21, which directly repressed PDCD4, and subsequently activated the JNK pathway, leading to the upregulation of ABCG2 in CRC cells. Inhibition of the JNK pathway overcame acquired 5-FU resistance both and .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-4292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867943PMC
January 2021

Author Correction: Threshold for neural tube defect risk by accumulated singleton loss-of-function variants.

Cell Res 2021 Apr;31(4):488

Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41422-021-00475-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115563PMC
April 2021

Correction to: Genetic analysis of Wnt/PCP genes in neural tube defects.

BMC Med Genomics 2021 Jan 27;14(1):29. Epub 2021 Jan 27.

Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic, Engineering at School of Life Sciences, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12920-021-00881-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841986PMC
January 2021

Loss-of-function or gain-of-function variations in VINCULIN (VCL) are risk factors of human neural tube defects.

Mol Genet Genomic Med 2021 02 24;9(2):e1563. Epub 2021 Jan 24.

Obstetrics & Gynecology Hospital, Institute of Reproduction & Development, Fudan University, Shanghai, China.

Background: Neural tube defects (NTDs) are severe birth defects resulting from the failure of neural tube closure during embryogenesis. Both genetic and environmental factors contribute to the occurrence of NTDs and the heritability of NTDs is approximately 70%. As a key component of focal adhesions, Vinculin (VCL) plays pivotal roles in cell skeleton remodeling and signal transduction. Vcl deficient mice displayed NTD, but how VCL variants contribute to human NTDs has not been addressed yet.

Methods: We screened VCL variants in a Chinese cohort of 387 NTDs and 244 controls by targeted next-generation sequencing.

Results: We identified four case-specific VCL variations (p.M209L, p.D256fs, p.L555V and p.R586Q). VCL p.D256fs and p.L555V are novel variations that have never been reported. Our analysis revealed that p.D256fs is a loss-of-function variant, while p.L555V showed a gain of function in planner cell polarity (PCP) pathway regulation and cell migration, probably due to its enhanced protein stability.

Conclusion: Our study reports human NTD specific novel variations in VCL and provides the functional evaluation of VCL variants related to the etiology of human NTDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077129PMC
February 2021

IL-37 Confers Anti-Tumor Activity by Regulation of m6A Methylation.

Front Oncol 2020 8;10:526866. Epub 2021 Jan 8.

Clinical Laboratory, Qingdao Central Hospital, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, China.

N6-methyladenosine (m6A) is a common transcriptomic modification in cancer. Recently, it has been found to be involved in the regulation of non-small cell lung cancer (NSCLC) formation and metastasis. Interleukin 37 (IL-37) plays a crucial protective role in lung cancer. In our previous studies, we found that IL-37 is a potential novel tumor suppressor by inhibiting IL-6 expression to suppress STAT3 activation and decreasing epithelial-to-mesenchymal transition. Moreover, we found that treatment of IL-37 in lung cancer cells induced widespread and dynamic RNA m6A methylation. The effects of RNA m6A methylation of IL-37 treatment require further study. However, the functions of RNA m6A methylation of IL-37 treatment still await elucidation. Using MeRIP-seq and RNA-seq, we uncovered a unique m6A methylation profile in the treatment of IL-37 on the A549 cell line. We also showed the expression of m6A writers METTL3, METTL14, and WTAP and erasers ALKBH5 and FTO in A549 cells and lung cancer tissues after the treatment of IL-37. This study showed that IL-37 could lead to changes in m6A methylation level and related molecule expression level in A546 cells and may downregulate the proliferation by inhibiting Wnt5a/5b pathway in A549 cells. We conclude that IL-37 suppresses tumor growth through regulation of RNA m6A methylation in lung cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.526866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821743PMC
January 2021

Clinicopathological features and risk factors analysis of lymph node metastasis and long-term prognosis in patients with synchronous multiple gastric cancer.

World J Surg Oncol 2021 Jan 21;19(1):20. Epub 2021 Jan 21.

Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, Jiangsu Province, China.

Background: As a common malignancy, gastric cancer (GC) remains an important threat to human's health. The incidence of synchronous multiple gastric cancer (SMGC) has increased obviously with technical advances of endoscopic and pathological examinations. Several studies have investigated the relationship between SMGC and solitary gastric cancer (SGC). However, little is known about the relationship between early and advanced SMGCs, and the independent risk factors of lymph node metastasis and prognosis in SMGC patients remain unclear.

Methods: We retrospectively collected 57 patients diagnosed as SMGC and underwent radical gastrectomies from December 2011 to September 2019. Epidemiological data and clinicopathological characteristics of all patients were recorded. Postoperative follow-up was performed by telephone or outpatient service. Chi-squared test or Fisher's exact test was adopted in analysis of categorical data. Continuous data were analyzed by using unpaired t test. Univariate and multivariate analyses were performed to investigate the independent risk factors of lymph node metastasis and tumor recurrence of SMGC.

Results: There were 45 males and 12 females. The average age was 62.1 years old. There were 20 patients with early SMGC and 37 patients with advanced SMGC. Most of patients (91.2%) had two malignant lesions. Tumor recurrence occurred in 8 patients, among which 7 patients died from recurrence. The rates of total gastrectomy, tumor size ≥ 2 cm, poorly differentiated type, lymph node metastasis, ulcer and nerve invasion, and preoperative CEA level were significantly higher in advanced SMGC patients compared to those with early SMGC. Lymphovascular cancer plug and preoperative CA125 were the independent risk factors of lymph node metastasis in patients with SMGC. Lymph node metastasis, nerve invasion, and preoperative AFP might be the risk factors of tumor recurrence of SMGC, but need further validation.

Conclusions: In patients with SMGC, the presence of tumor size ≥ 2 cm, poorly differentiated type, lymph node metastasis, ulcer, nerve invasion, and relatively high preoperative CEA level might indicate the advanced SMGC. More attention should be paid to lymph node metastasis in SMGC patients with lymphovascular cancer plug and high preoperative CA125. Lymph node metastasis, nerve invasion, and preoperative AFP might be associated with recurrence of SMGC, needing further validation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12957-021-02130-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819186PMC
January 2021

Exploring Natural Allelic Variations of the β-Triketone Herbicide Resistance Gene HIS1 for Application in indica Rice and Particularly in Two-Line Hybrid Rice.

Rice (N Y) 2021 Jan 7;14(1). Epub 2021 Jan 7.

State Key Laboratory of Hybrid Rice, Hunan Hybrid Rice Research Center, Changsha, China.

Background: Benzobicyclon (BBC) is a β-triketone herbicide (bTH) used in rice paddy fields. It has the advantages of high efficiency, low toxicity, high crop safety, and good environmental compatibility, and shows efficacy against paddy weeds resistant to other types of herbicides. However, as some important indica rice varieties are susceptible to BBC, BBC is currently only registered and applied in japonica rice cultivation areas.

Results: By analyzing haplotypes of the bTHs broad-spectrum resistance gene HIS1 and phenotypes for BBC in 493 major indica rice accessions in China, we identified a novel non-functional allelic variant of HIS1 in addition to the previously reported 28-bp deletion. Through detection with markers specific to the two non-functional mutations, it was clear that 25.4% of indica conventional varieties, 59.9% of fertility restorers, and 15.9% of sterile lines were susceptible to BBC. In addition, due to natural allelic variations of the HIS1 gene in the sterile and restorer lines, some two-line hybrid sterile lines were sensitive to bTHs, and the corresponding restorers were resistant. We showed the potential effectiveness of using bTHs to address the issue of two-line hybrid rice seed purity stemming from the self-crossing of sterile lines during hybrid rice seed production. Finally, allelic variations of the HIS1 gene may also play an important role in the mechanized seed production of hybrid rice.

Conclusions: Our findings offer guidance for the application of BBC in indica rice areas and provide a non-transgenic approach to address the seed purity issue of two-line hybrid rice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12284-020-00448-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790941PMC
January 2021

Identification of Core Genes Involved in the Metastasis of Clear Cell Renal Cell Carcinoma.

Cancer Manag Res 2020 30;12:13437-13449. Epub 2020 Dec 30.

Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China.

Introduction: Renal cell carcinoma (RCC) is one of the most common malignancies globally, among which clear cell carcinoma (ccRCC) accounts for 85-90% of all pathological types. This study aims to screen out potential genes in metastatic ccRCC so as to provide novel insights for ccRCC treatment.

Methods: GSE53757 and GSE84546 datasets in the Gene Expression Omnibus (GEO) were profiled to identify differentially expressed genes (DEGs) from ccRCC samples with or without metastasis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and the gene ontology (GO) analysis were performed to analyze pathway enrichment and functional annotation of DEGs. Protein-protein interaction (PPI) network was constructed, and survival analysis was conducted to evaluate the clinical values of the identified hub genes. In vitro loss-of-function assays were performed to explore the biological roles of these genes.

Results: The bioinformatic analysis indicated that 312 DEGs were identified, including 148 upregulated genes and 164 downregulated ones. Using PPI and Cytoscape, 10 hub genes were selected (, , , , , , , , , and ) from DEGs which might be closely related with ccRCC metastasis. In Kaplan-Meier analysis, three potential prognostic biomarkers (, and ) were identified. Finally, cell proliferative and invasive assays further verified that , and were associated with the proliferation and invasion of ccRCC cells.

Conclusion: Our results demonstrated that metastatic ccRCC was partially attributed to the aberrant expression of , and , and more personalized therapeutic approaches should be explored targeting these hub genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S276818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779301PMC
December 2020

Qualitative Analyses of the Reasons Why Patients Do Not Attend Scheduled Inpatient Appointments in a Hospital in Guangzhou, China.

Risk Manag Healthc Policy 2020 7;13:2857-2865. Epub 2020 Dec 7.

School of Nursing, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.

Purpose: Exploration of the reasons why people miss scheduled inpatient appointments from the perspectives of patients.

Methods: Semi-structured interviews via telephone were conducted with patients who missed their inpatient appointments. Data were analyzed based on Colaizzi's seven-step method.

Results: Twenty-five patients and five dependents were enrolled. Three themes were identified: practical barriers, lack of knowledge about the disease, and negative emotional responses. Personal social obligations, state of illness, financial issues and long waiting times were the main practical barriers preventing patients from attending their inpatient appointment. Patients' perceptions of feasible self-solving symptoms, readily believing people around them, and a blindly optimistic attitude towards disease contributed to their insufficient knowledge about the disease. Negative emotional responses (eg, sense of fear and lack of trust in physicians) had a detrimental effect on inpatient attendance.

Conclusion: Three main factors contributed to non-attendance of inpatient appointments: practical barriers, lack of knowledge about disease, and negative emotional response. Our study provides new, valuable evidence on non-attendance of inpatient appointments in China. Our findings could offer meaningful insights into developing effective strategies to reduce non-attendance of inpatient appointments in other countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/RMHP.S280665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733034PMC
December 2020

An autoregulatory feedback loop of miR-21/VMP1 is responsible for the abnormal expression of miR-21 in colorectal cancer cells.

Cell Death Dis 2020 12 14;11(12):1067. Epub 2020 Dec 14.

College of Life Sciences, Sichuan University, Chengdu, Sichuan, P.R. China.

MircoRNA-21 (miR-21) was found to be highly expressed in various solid tumors, and its oncogenic properties have been extensively studied in recent years. However, the reason why miR-21 is highly expressed in various tumors remains elusive. Here, we found that the expression of miR-21 was negatively correlated with the expression of vacuole membrane protein-1 (VMP1) in colorectal cancer. Transcription of VMP1 activated either by small activating RNA (saRNA) or transcriptional activator GLI3 inhibited miR-21 expression through reducing its transcripts of VMP1-miR-21 and pri-miR-21, while no significant change in miR-21 expression after exogenous overexpression VMP1 in colorectal cancer cell HCT116. Considering the overlapping location of VMP1 and miR-21 gene in genome, the result suggested that the transcription of miR-21 was inhibited by the endogenous transcriptional activation of VMP1. Furthermore, we identified that miR-21 inhibited the activation and nuclear translocation of transcription factor EB (TFEB) through reducing the inhibitory of PTEN on AKT phosphorylation, which can directly activate the transcription of VMP1. Loss of miR-21 significantly increased VMP1 expression, which could be blocked by PTEN inhibitor (VO-Ohpic) or TFEB siRNA. These results showed that miR-21 negatively regulated VMP1 transcription through the PTEN/AKT/TFEB pathway, and TFEB-induced transcriptional activation of VMP1 could inhibit miR-21 expression, thus forming a feedback regulatory loop of miR-21/VMP1. We further found that disrupting the miR-21/VMP1 feedback loop will decrease the expression of miR-21, reduce the malignancy, and increase their sensitivity to 5-fluorouracil in colorectal cancer cells. Taken together, our results revealed a novel regulatory mechanism of miR-21 expression, and targeting the miR-21/VMP1 feedback loop may provide a new approach to inhibit miR-21 expression in colorectal cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-03265-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736343PMC
December 2020

Identification of ribosomal protein family in triple-negative breast cancer by bioinformatics analysis.

Biosci Rep 2021 01;41(1)

Department of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.

Triple-negative breast cancer (TNBC) accounts for ∼20% of all breast cancer (BC) cases. The management of TNBC represents a challenge due to its worse prognosis, heterogeneity and lack of targeted therapy. Moreover, its mechanisms are not fully clear. The aim of the study is to identify crucial genes between TNBC and non-TNBC for underlying targets for diagnostic and therapeutic methods of TNBC. The differentially expressed genes (DEGs) between TNBC and non-TNBC were selected from the Gene Expression Omnibus (GEO) database after the integrated analysis of two datasets (GSE65194 and GSE76124). Then Gene ontology (GO) and KEGG analysis were performed by DAVID database, protein-protein interaction (PPI) of DEGs was constructed by Search Tool for the Retrieval of Reciprocity Genes (STRING) database. Furthermore, centrality analysis and module analysis were carried out by Cytoscape to analyze the TNBC-related PPI. Subsequently, overall survival (OS) analysis was performed by GEPIA. Finally, the expressions of these key genes in TNBC and non-TNBC tissues were tested by qRT-PCR. The results showed that 955 DEGs were obtained, which were mainly enriched in ribosome, ribosomal subunit, and so on. Moreover, 19 candidate genes were focused on by centrality analysis and module analysis. Furthermore, we found the low expressions of ribosomal protein S9 (RPS9), ribosomal protein S14 (RPS14), ribosomal protein S27 (RPS27), ribosomal protein L11 (RPL11) and ribosomal protein L14 (RPL14) were related to a poor OS in BC patients. Additionally, qRT-PCR results suggested that these five genes were notably down-regulated in TNBC tissues. In summary, the present study suggests that ribosomal proteins are related to TNBC, and they may play an important role in the diagnosis, treatment and prognosis of TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BSR20200869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789804PMC
January 2021

Bacteria-derived membrane vesicles to advance targeted photothermal tumor ablation.

Biomaterials 2021 01 24;268:120550. Epub 2020 Nov 24.

Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu, 215123, China. Electronic address:

Nanoscale outer membrane vesicles (OMVs) secreted by Gram-negative bacteria are often applied in antibacterial treatment as adjuvants or antigens. Recently, OMVs have also been tested in a few anti-tumor treatment studies, in which OMVs are injected multiple times to achieve certain therapeutic effects, showing risks in repeated cytokine storms. Herein, we propose the use a single low dose of OMVs combined with photothermal therapy (PTT) for effective cancer treatment. It was found that single i. v. injection of OMVs could activate the immune system by boosting the secretion levels of anti-tumor related cytokines. In addition, single i. v. injection of OMVs could also lead to extravasation of red blood cells in the tumor mainly owing to the effect of lipopolysaccharide on the OMVs. Such effect was not observed in other normal organs. As the results, the tumors on OMV-treated mice showed obviously darkened color with greatly increased intratumoral optical absorbance in the near-infrared (NIR) region, further enabling effective photothermal ablation of those tumors by the NIR laser. Without causing obvious adverse responses, bacteria-derived OMVs may be a new type of therapeutic agent for cancer treatment with multiple functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2020.120550DOI Listing
January 2021

GIT1 overexpression promotes epithelial-mesenchymal transition and predicts poor prognosis in hepatocellular carcinoma.

Bioengineered 2021 12;12(1):30-43

Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University , Yangzhou, Jiangsu, P.R. China.

Globally, hepatocellular carcinoma (HCC) is one of the most common causes of cancer-associated mortalities. It has a high rate of metastasis and recurrence, which predict a poor prognosis. G-protein-coupled receptor (GPCR)-kinase interacting protein-1 (GIT1) is a multifunctional scaffold protein that mediates the progression of various tumors. Studies have correlated GIT1 with HCC, however, these correlations have not been fully elucidated. Therefore, we aimed at evaluating the expression of GIT1 in HCC tissues and cells, and to investigate its role and potential mechanisms in HCC progression. The expression levels of GIT1 in HCC tissues and other cancers was determined by using the Oncomine and TCGA databases. Functional analysis of GIT1 in HCC was evaluated through and experiments, whereby, HCC cells were transfected with synthetically overexpressed and short hairpin RNA (shRNA) lentivirus-mediated plasmids. Kaplan-Meier and Cox regression methods were used to establish the associations between GIT1 and clinical outcomes of 158 HCC patients. GIT1 was found to be elevated in HCC tissues where it promoted the invasion, migration, and proliferation of HCC cells. Moreover, the overexpression of GIT1 prompted epithelial-mesenchymal transition (EMT) by activating extracellular regulated kinase 1/2 (ERK1/2) pathway, which was shown to be reversed by SCH772984, a specific ERK1/2 inhibitor. GIT1 was also found to be associated with malignant features of HCC, leading to a poorer prognosis. In conclusion, GIT1 promotes HCC progression by inducing EMT and may reflect the course of HCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21655979.2020.1855914DOI Listing
December 2021
-->